title: Structural basis for G.C recognition in the DNA minor groove.
abstract: Small molecules that target specific DNA sequences offer a potentially general approach for the regulation of gene expression. Pyrrole-imidazole polyamides represent the only class of synthetic small molecules that can bind predetermined DNA sequences with affinities and specificities comparable to DNA binding proteins. Antiparallel side-by-side pairings of two aromatic amino acids, imidazole (Im) and pyrrole (Py), distinguish G.C from C.G, and both from A.T/T.A base pairs. A high resolution X-ray crystal structure of a four-ring pyrrole-imidazole polyamide specifically bound as a dimer to a six-base pair predetermined DNA site reveals a structural framework of hydrogen bonds and interactions with the walls of the minor groove that underlies the pairing rules for DNA recognition.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Kielkopf
authors.forename: E E
authors.initials: EE
authors.lastname: Baird
authors.forename: P B
authors.initials: PB
authors.lastname: Dervan
authors.forename: D C
authors.initials: DC
authors.lastname: Rees
mesh_terms: D001482:Base Composition; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D003854:Deoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D019281:Dimerization; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011758:Pyrroles / Q000737:chemistry
chemical_list: D003854:Deoxyribonucleotides; D007093:Imidazoles; D011758:Pyrroles; D004247:DNA